Metal-organic frameworks (MOFs) are widely studied for biomedical applications, particularly in nanoscale drug delivery. However, reproducibility remains a major challenge in MOF research, including batch-to-batch variations, differences in synthetic and analytical practices, and a lack of data sharing. This perspective highlights common issues affecting reproducibility in MOF-based nanomedicine, such as variability in synthesis and characterization practices, and suggests best practices for improving reproducibility. MOFs, with their high surface area and tunable properties, are promising for drug delivery, but their synthesis is complex and often yields low quantities of the desired phase. An inter-laboratory study showed that only one lab could reproduce a pure phase of a Zr-porphyrin MOF, highlighting the difficulty in achieving consistent results. Multiple MOF phases can exist for a given metal-ligand system, and identifying the correct phase is crucial for biological applications. For example, UiO-66, a common MOF, has multiple phases with different structures, and misidentification can lead to incorrect conclusions. Synthesis of MOFs requires precise control over parameters such as temperature, time, and pH to ensure reproducibility. Variations in these parameters can lead to differences in particle size, morphology, and surface chemistry, which affect biological behavior. Comprehensive characterization of MOFs is essential, including techniques like X-ray diffraction, electron microscopy, and gas adsorption measurements, to ensure accurate identification and understanding of MOF properties. In vitro studies also face reproducibility challenges, including variability in cell lines, assay methods, and data reporting. False positives can occur in toxicity assays if MOFs aggregate, and real-time cell analysis is more reliable for detecting changes in cell behavior. Proper control experiments and detailed data sharing are necessary to ensure reproducibility. The lack of standardized protocols and data sharing in MOF research hinders reproducibility. Efforts to create standardized data archives and promote open access to raw data are essential for advancing the field. The first MOFs are now undergoing human trials, underscoring the need for reproducibility and transparency in MOF research to ensure successful clinical translation. Interdisciplinary collaboration and adherence to best practices are crucial for advancing MOF-based nanomedicine.Metal-organic frameworks (MOFs) are widely studied for biomedical applications, particularly in nanoscale drug delivery. However, reproducibility remains a major challenge in MOF research, including batch-to-batch variations, differences in synthetic and analytical practices, and a lack of data sharing. This perspective highlights common issues affecting reproducibility in MOF-based nanomedicine, such as variability in synthesis and characterization practices, and suggests best practices for improving reproducibility. MOFs, with their high surface area and tunable properties, are promising for drug delivery, but their synthesis is complex and often yields low quantities of the desired phase. An inter-laboratory study showed that only one lab could reproduce a pure phase of a Zr-porphyrin MOF, highlighting the difficulty in achieving consistent results. Multiple MOF phases can exist for a given metal-ligand system, and identifying the correct phase is crucial for biological applications. For example, UiO-66, a common MOF, has multiple phases with different structures, and misidentification can lead to incorrect conclusions. Synthesis of MOFs requires precise control over parameters such as temperature, time, and pH to ensure reproducibility. Variations in these parameters can lead to differences in particle size, morphology, and surface chemistry, which affect biological behavior. Comprehensive characterization of MOFs is essential, including techniques like X-ray diffraction, electron microscopy, and gas adsorption measurements, to ensure accurate identification and understanding of MOF properties. In vitro studies also face reproducibility challenges, including variability in cell lines, assay methods, and data reporting. False positives can occur in toxicity assays if MOFs aggregate, and real-time cell analysis is more reliable for detecting changes in cell behavior. Proper control experiments and detailed data sharing are necessary to ensure reproducibility. The lack of standardized protocols and data sharing in MOF research hinders reproducibility. Efforts to create standardized data archives and promote open access to raw data are essential for advancing the field. The first MOFs are now undergoing human trials, underscoring the need for reproducibility and transparency in MOF research to ensure successful clinical translation. Interdisciplinary collaboration and adherence to best practices are crucial for advancing MOF-based nanomedicine.